Actualizado Reviewed

Prepregnancy Counseling and Care for People of Childbearing Age with HIV

Overview

Panel's Recommendations
  • Discuss reproductive desires and plans with all people with HIV who are of childbearing potential on an ongoing basis throughout the course of their care (AIII).
  • Provide information about effective and appropriate contraceptive methods to people who do not currently desire pregnancy (AI). Offer all contraceptive methods or refer for contraceptive services. Individuals with HIV can use all available contraceptive methods (e.g., pill, patch ring, injection, implant); however, the presence of other medical co-morbidities and drug -drug interactions between hormonal contraceptives, antiretroviral (ARV) drugs, and other medications should be considered (see Table 3) (AII). This information may help support shared decision-making about acceptable contraception options for people not currently desiring pregnancy.
  • During prepregnancy counseling, provide information on safer sex and ask about the use of alcohol, nicotine products, and other substances. Provide or refer to evidence-based interventions for substance use disorder, including medication-assisted treatment for opioid use disorder (e.g., methadone, buprenorphine), and counsel people on how to manage health risks (e.g., by accessing a syringe services program) when indicated. (AII).
  • Provide education and counseling about interventions to prevent perinatal HIV transmission, including antiretroviral therapy (ART). Explain that people with HIV should attain maximum viral suppression before attempting conception, for their own health, to prevent sexual HIV transmission to partners without HIV (AI), and to minimize the risk of in utero HIV transmission to the infant (AI). When fully suppressive ART is started before pregnancy and undetectable viral load is maintained throughout pregnancy and at delivery, the risk of HIV transmission to the infant is extremely low (<1%).
  • For people with HIV who are considering or planning a pregnancy, begin to provide patient-centered, evidence-based counseling to support shared decision making about infant feeding (AIII) (see Infant Feeding for Individuals with HIV in the United States).Information and plans for infant feeding should be reviewed throughout pregnancy and again after delivery.
  • When selecting or evaluating an ARV regimen for people of childbearing potential with HIV, consider a regimen’s effectiveness, changes in ARV pharmacokinetics in the second and third trimesters of pregnancy, a person’s hepatitis B status, and the possible adverse outcomes for the pregnant person and their fetus (AII). See Teratogenicity and Recommendations for Use of Antiretroviral Drugs During Pregnancy: Overview for more information. The Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission emphasizes the importance of counseling and shared decision-making regarding all ARV regimens for people with HIV (AIII).
Rating of Recommendations: A = Strong; B = Moderate; C = Optional

Rating of Evidence: I = One or more randomized trials with clinical outcomes and/or validated laboratory endpoints; II = One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = Expert opinion

Overview

The Centers for Disease Control and Prevention (CDC), the American College of Obstetricians and Gynecologists (ACOG), and other national organizations recommend offering all people of childbearing potential comprehensive family planning and the opportunity to receive prepregnancy counseling and care as a component of routine primary medical care. The purpose of prepregnancy care is to improve the health of each person before conception by identifying risk factors for adverse outcomes for the pregnant person and their fetus, tailoring education and counseling to individual needs, and treating or stabilizing medical conditions to optimize outcomes for the pregnancy and the fetus/newborn.1,2 Prepregnancy care is not something that occurs in a single clinical visit; rather, it requires integrating ongoing care and interventions into primary care to address people’s needs during the different stages of reproductive life. Integrating comprehensive family planning and prepregnancy care into routine health care visits can help people with HIV reach their desired reproductive outcomes by supporting them to make informed decisions about their fertility and contraceptive use that are aligned with their preferences and reproductive goals.3-6 Providers should initiate and document a nonjudgmental conversation with all people of reproductive age about their reproductive desires because they may be reluctant to bring up the subject themselves.7-11

A meta-analysis of 50 studies found a 42% prevalence of fertility desire among people with HIV. In a pooled analysis, fertility desire was associated with being on antiretroviral therapy (ART), male sex, age younger than 30, being married or cohabitating, a secondary education or higher, and being childless.12 In a retrospective study among 255 women with HIV, 69 (27.1%) reported an intended pregnancy. Those with intended pregnancies were more likely to be older, White, married, privately insured, and college educated. They were less likely than those with unintended pregnancies to use tobacco, alcohol, opiates, or cocaine during pregnancy, more likely to disclose their HIV status to the father of the baby by delivery, and more likely to receive less effective contraception (e.g., condoms) postpartum. In a multivariate analysis, pregnancy intendedness was an important predictor of nondetectable viral load at pregnancy entry but not at delivery.13 Pregnancy intentions may not be binary and may change over time, thus underscoring the need for health care providers to engage in ongoing discussions to support dynamic pregnancy intentions.11

Health care providers who routinely care for people of reproductive age with HIV play an important role in promoting prepregnancy health and informed reproductive decisions. However, even among providers who offer primary care to people with HIV, the delivery of comprehensive reproductive counseling often falls short of the current guidelines.14-16

The fundamental principles of prepregnancy counseling and care are outlined in the CDC Preconception Care Work Group’s Recommendations to Improve Preconception Health and Health Care. In addition to the general components of prepregnancy counseling and care that are appropriate for all people of reproductive age, people with HIV have specific needs that should be addressed.17-20

  • Discuss reproductive options; actively assess their pregnancy intentions on an ongoing basis throughout the course of care; and, when appropriate, make referrals to HIV and reproductive health specialists, including experts in reproductive endocrinology and infertility when necessary. The HIV status of one or both parents should not be a reason to withhold standard of care infertility treatment and assist individuals and couples in reaching their desired reproductive outcomes.
  • Offer all people who currently do not desire pregnancy a full range of contraceptive methods to help them achieve their fertility goals. People with HIV can use all available contraceptive methods, including hormonal contraception (e.g., pill, patch, ring, injection, implant) and intrauterine devices (IUDs); see Medical Eligibility Criteria for Contraceptive Use and the updated summary chart.21 Providers should be aware of the presence of other medical co-morbidities and potential interactions between antiretroviral (ARV) drugs, hormonal contraceptives, and other medications that could lower contraceptive efficacy or increase the risk of such adverse effects as blood clots (see Table 3 below).
  • Offer emergency contraception as appropriate, including emergency contraceptive pills and IUDs (see the ACOG Practice Bulletin on Emergency Contraception). Emergency contraceptive pills that contain estrogen and progestin and those that only contain levonorgestrel (LNG) may have interactions with ARV drugs that are similar to the ones observed with combined oral contraceptives.22 AIDS Clinical Trials Group (ACTG) 5375 showed that doubling the dose of LNG from 1.5 mg to 3 mg in women receiving efavirenz (EFV)-based ART helped overcome the drug–drug interaction with this ARV.23,24 No data are available on potential interactions between ARV drugs and ulipristal acetate, a progesterone receptor modulator; however, ulipristal acetate is metabolized predominantly by cytochrome P450 (CYP) 3A4, so interactions may occur (see the HIV Drug Interaction Checker).
  • Use the prepregnancy period to modify the ARV regimen for people who are contemplating pregnancy to optimize virologic suppression and minimize potential adverse effects (see Recommendations for Use of Antiretroviral Drugs During Pregnancy and Table 7). Recognize that individuals with perinatally acquired HIV may have special needs (e.g., psychosocial support, adherence support)25 (see Prenatal Care, Antiretroviral Therapy, and HIV Management in People with Perinatally Acquired HIV Infection).
  • Recognize that transgender and gender-diverse people who were assigned female sex at birth may have special needs.26 For transgender men attempting pregnancy, the use of testosterone may induce hypothalamic–pituitary–gonadal suppression, leading to decreased ovulation.27
  • Recognize that the primary treatment goal for people with HIV who are planning a pregnancy should include sustained suppression of plasma viral load below the limit of detection before conception for their own health, to minimize the risk of perinatal HIV transmission, and to prevent sexual HIV transmission to a partner without HIV (see Reproductive Options for Couples When One or Both Partners Have HIV). Inform individuals who are considering or planning pregnancy that with ART started before pregnancy and an undetectable viral load maintained throughout pregnancy and delivery, their risk of HIV transmission to the infant is extremely low (<1%).28,29
  • Explain that people with HIV who take ART as prescribed and who achieve and maintain an undetectable viral load will not transmit HIV through sex, commonly known as Undetectable = Untransmittable or U=U. For more information, see Let’s Stop HIV Together.
  • Encourage individuals to disclose their HIV status to their partner or co-parent before pregnancy if doing so is safe. However, this disclosure should not be a requirement of assisting couples in achieving pregnancy.
  • Encourage sexual partners to receive HIV counseling and testing so that they can seek HIV care if they have HIV or seek advice about HIV prevention, including pre-exposure prophylaxis (PrEP), if they do not have HIV (see Pre-exposure Prophylaxis (PrEP) to Reduce the Risk of Acquiring HIV During Periconception, Antepartum, and Postpartum Periods).
  • Ask about the use of alcohol, tobacco, and other substances. Provide or refer to evidence-based interventions for substance use disorder, including medication-assisted treatment for opioid use disorder (e.g., methadone, buprenorphine), and counsel people on how to manage health risks (e.g., access to a syringe services program). A 2019 analysis30 reported that overall, 39% of women with HIV of reproductive age reported current drinking and 10% reported binge drinking. Compared to non-drinkers, binge drinkers were less likely to adhere to ART or be virally suppressed and more likely to smoke and use drugs. Between 2007 and 2019, marijuana use during pregnancy among women with HIV increased from 7.1% to 11.7%, whereas alcohol and opioid use were unchanged. Postpartum alcohol (44.4%), marijuana (13.6%), and concomitant alcohol and marijuana (10%) use were common; marijuana use increased from 10.2% in 2006 to 23.7% in 2019, whereas postpartum alcohol use was unchanged.31
  • Counsel on maintaining a healthy diet and healthy weight before and during pregnancy.
  • Counsel people who are contemplating pregnancy to take a daily multivitamin that contains 400 mcg of folic acid to help prevent neural tube defects (NTDs). Individuals with a history of having a child with NTDs, with a family history of NTDs, or on certain anti-epileptic medications, especially valproic acid, are candidates for receiving a higher dose (1,000–4,000 mcg) of folic acid. Higher doses of folate may also be considered for people receiving trimethoprim/sulfamethoxazole who are trying to conceive (see Special Considerations in Pregnancy in Pneumocystis Pneumonia).
  • Optimize the health of people with HIV prior to pregnancy (e.g., ensure appropriate folate intake, test for all sexually transmitted infections and treat as indicated, consider the teratogenic potential of all prescribed medications, and consider switching to safer medications).
  • Educate and counsel about the risk factors for perinatal HIV transmission, the strategies to reduce those risks, and the potential effects HIV or taking ARV drugs during pregnancy may have on the course of pregnancy and health outcomes for the pregnant person and fetus.
  • Support shared decision-making about ART. Educate and counsel on the factors that affect the selection of ARVs for people who are trying to conceive, are pregnant, or are postpartum. For more information, see Recommendations for Use of Antiretroviral Drugs During Pregnancy: Overview.
  • Consider the following factors when prescribing ART to people of childbearing potential: the regimen’s effectiveness, changes in ARV pharmacokinetics (PK) in the second and third trimesters of pregnancy, an individual’s hepatitis B virus (HBV) status, possible adverse outcomes for the pregnant person and their fetus, and the likelihood of developing drug resistance.32-34
  • Provide patient-centered, evidence-based counseling to support shared decision-making about infant feeding (see Infant Feeding for Individuals with HIV in the United States). Information about and plans for infant feeding should be reviewed throughout pregnancy and again after delivery.
  • Evaluate and manage ART-associated adverse effects (e.g., hyperglycemia, anemia, hepatotoxicity) that may affect health outcomes for the pregnant person and fetus.
  • Administer all vaccines as indicated (see CDC’s Recommended Immunization Schedule and ACOG Maternal Immunization Practice Advisory 2022), which includes vaccination for influenza, pneumococcus, HBV, tetanus, and SARS-CoV-2.35 All people, including those with HIV, should receive Tdap (tetanus, diphtheria, and pertussis) vaccination during each pregnancy, typically between 27 and 36 weeks of gestation but preferably as early in this time window as possible.
  • Ask pregnant people whether they feel safe at home and offer assistance or referrals for those experiencing intimate partner violence (IPV) or requesting assistance.

Drug–Drug Interactions Between Hormonal Contraceptives and Antiretroviral Therapy 

Data on drug interactions between ARVs and hormonal contraceptives primarily come from drug labels and several studies on the PK and pharmacodynamics among the different forms of contraception and ARVs.22,36-59 The contraceptive effectiveness of the LNG IUD is largely through local (i.e., intrauterine) release of LNG, not through systemic absorption. CDC’s U.S. Medical Eligibility Criteria for Contraceptive Use lists the LNG IUD as category 1 (no restrictions) in drug interactions with all ARVs in women who already have an IUD and category 1/2 (benefits outweigh risk) for those initiating the use of an IUD. 

Hormonal contraceptives can be used with ARVs in people with HIV without other contraindications. The contraception effect is usually attributable to the progestin component of contraceptives. Drug interactions that decrease concentrations of the progestin component may affect contraceptive efficacy. An alternative or additional contraceptive method may be recommended when drug interactions are known. For people receiving darunavir/ritonavir (DRV/r)-based ART, an alternative or additional contraception may be considered because the area under the curve (AUC) for oral contraceptive hormones may be decreased.60 Cobicistat-boosted protease inhibitors (PIs) are contraindicated with drosperinone-containing hormonal contraceptives due to the potential for hyperkalemia.54 Depot medroxyprogesterone acetate (DMPA) can be used without restriction because of its relatively higher dose than other progesterone-based contraception, and limited studies have shown no significant interaction between DMPA and ARVs.37,39,49,61 

Several studies have shown that the use of EFV decreases the effectiveness of hormonal implants and hormonal vaginal rings. Although contraceptive implants (e.g., etonogestrel [ENG], LNG) generally can be used in people who are receiving ARVs, both PK and clinical data suggest that these implants have decreased efficacy when used with EFV-based regimens.47,62-64 LNG implants are not available in the United States. A PK evaluation reported that the geometric mean ratios of LNG concentrations (patients taking EFV-based ART vs. ART-naive patients) were 0.53 at 24 weeks and 0.43 at 48 weeks. Three pregnancies occurred in the EFV group (15%) between Week 36 and Week 48, whereas no pregnancies occurred in the ART-naive or nevirapine (NVP) groups.51

In a study of 570 women with HIV in Eswatini, formerly known as Swaziland, who had LNG implants (i.e., Jadelle), none of the women on NVP- or lopinavir/ritonavir-based regimens (n = 208 and n = 13, respectively) became pregnant, whereas 15 women on EFV (n = 121; 12.4%) became pregnant.47 A prospective study in seven African countries collected data from 5,153 women with HIV who were followed for 1 to 3 years. During the follow-up period, 40% used injectables, 14% used oral contraceptives, and 9% of the women used implants (mostly LNG); 31% of these women took ART during the follow-up period, mostly NVP-containing (75%) or EFV-containing (15%) regimens. Among women who were not using contraception, pregnancy rates were 13.2 per 100 person-years for those who were on ART and 22.5 per 100 person-years for those who were not on ART. Implants greatly reduced the incidence of pregnancy among women on ART (adjusted hazard ratio [aHR] 0.06; 95% confidence interval [CI], 0.01–0.45) and women who were not on ART (aHR 0.05; 95% CI, 0.02–0.11). Injectables and oral contraceptives also reduced pregnancy risk but to lesser degrees. A potential lesser degree of effectiveness of these methods may be due to their greater dependence on user action, as compared to longer acting methods. ART use did not significantly diminish contraceptive effectiveness, although all methods showed nonsignificant reduced contraceptive effectiveness when people used EFV concurrently.65 

In a retrospective study among 1,152 women with HIV using either EFV or NVP and ENG or LNG implants, 115 pregnancies occurred, yielding a pregnancy incidence rate of 6.32 (5.27–7.59), with a rate of 9.26 and 4.74 among ENG and LNG implant users, respectively. Pregnancy incidence rates did not differ between EFV- and NVP-based regimens (incidence rate ratio [IRR] = 1.00; 95% CI, 0.71–1.43). No pregnancies were recorded among women on PI-based regimens. Pregnancy rates of EFV- and NVP-containing regimens were similar at 6.41 (4.70–8.73) and 6.44 (5.13–8.07), respectively. Pregnancy rates differed by implant type with LNG implant users half as likely to become pregnant as ENG implant users (IRR = 0.51; 95% CI, 0.33–0.73; P > 0.01).66 A study of 42 women in Malawi (30 women with HIV on EFV and LNG, and 12 women without HIV on LNG) showed that EFV users had lower LNG concentrations that non-EFV users, and one-third of the EFV/LNG users had LNG concentrations <180 pg/mL, which is the suggested minimum level for efficacy. No pregnancies were reported over 60 women-years of follow-up.67 

In a non-randomized, open label, parallel group, longitudinal pharmacokinetic study among Ugandan women aged 18 to 45, participants with HIV who were on EFV 600 mg received double-dose 300-mg LNG implants and were compared to women without HIV who received standard-dose 150-mg LNG implants. Plasma LNG concentration was quantified more than 48 weeks after implant insertion. LNG AUC from 0 to 24 weeks was 34% lower among women taking 300-mg LNG plus ART versus women taking 150-mg LNG (geometric mean 9,998 vs. 15,231 pg•week/mL, respectively). Double-dose LNG implants did not completely overcome the drug–drug interaction with EFV58; therefore, prescribing double-dose LNG implants is not recommended to overcome this drug–drug interaction. Since ovulatory activity was noted among women taking 300-mg LNG plus ART, another contraceptive method that does not interact with EFV is needed. 

Genetic contributions also may influence observed drug–drug interactions between contraceptives and ARVs. In a study of 19 women not on ART (control group), 19 women on EFV, and 19 women on NVP, all received ENG implants. Women in the EFV group with CYP2B6 516 G>T had 43% lower ENG minimum plasma concentration (Cmin) and 34% lower AUC from 0 to 24 hours postdose (AUC0–24) at 24 weeks. For women on NVP, those with NR1I2 63396 C>T had lower ENG Cmin and 37% lower AUC0–24 at 24 weeks.55 A PK study reported that EFV reduced the median ENG level by at least 93% in CYP2B6 slow metabolizers versus 75% in normal and intermediate metabolizers. EFV reduced median ethinyl estradiol (EE) concentration by 75% in slow metabolizers and 41% in normal and intermediate metabolizers among women using hormonal vaginal ring contraceptives.68

Tuberculosis Treatment, Antiretrovirals, and Contraception 

Other medications, such as concomitant tuberculosis (TB) treatment and ARVs, may also have drug–drug interactions with contraceptives. A PK study of DMPA among women with HIV/TB coinfection who received EFV-based HIV treatment and rifampicin-based TB treatment showed that among 42 evaluable women, 5 women (11.9%; 95% CI, 4.0% to 25.6%) had medroxyprogesterone acetate (MPA) <0.1 ng/mL at Week 12, the level above which ovulation is prevented; of these women, 1 had MPA <0.1 ng/mL at Week 10. The median clearance of MPA was higher in women on EFV compared with women with HIV who were not on ART, thus leading to subtherapeutic concentrations of MPA in 12% of women at Week 12.69 After performing PK modeling with DMPA and ART, the authors of this study suggested redosing DMPA more frequently,70 such as every 8 to 10 weeks. In a PK study of the interaction between DMPA, EFV, rifampicin, and isoniazid (INH) during treatment for HIV and tuberculosis, there were no associations between either CYP2B6 or N-acetyltransferase 2 genotype and MPA Cmin at Week 12. The study was not designed to distinguish inductive effects of rifampicin from possible inhibitory effects of INH on MPA clearance.

Nevertheless, the authors recommended that more frequent DMPA dosing may be appropriate for women receiving all these medications.71

Long-Acting Cabotegravir

In a secondary analysis of 85 cisgender women enrolled in HPTN 077, compared to women reporting no hormonal contraception (n = 6), oral contraceptive use (n = 18) was associated with lower long-acting cabotegravir (CAB-LA) peak concentration but was not associated with other PK parameters, suggesting this association is not likely to be clinically significant. No other hormonal contraceptive type (injectable, implants, and other) was associated with significant differences in CAB-LA PK parameters.72

Vaginal Ring 

A new contraceptive vaginal ring containing segesterone/EE (Annovera) has recently been approved by the U.S. Food and Drug Administration. No available drug–drug interaction studies with this contraceptive vaginal ring and ARV and CYP inducers/inhibitors are known. The contraceptive may possibly be metabolized in the same way as ENG and EE in the NuvaRing (see Table 3 below).57 

Table 3 

Because data are limited on pregnancy rates among people on different hormonal contraceptives and ARVs, some of the dosing recommendations in Table 3 are based on consensus expert opinion. Whenever possible, the recommendations are based on available data regarding PK interactions between ARVs and combined hormonal methods, DMPA, and LNG and ENG implants. The smallest decrease in PK for which an alternative method was recommended was a 14% decrease in norethindrone (with DRV/r). The Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission does not recommend any change in EE dose in people who are receiving etravirine (EE increased 22%) or rilpivirine (EE increased 14%).   

Table 3. Drug Interactions Between Antiretroviral Agents and Hormonal Contraceptives

Note: All recommendations in this table are based on consensus expert opinion. Additional information can be found in CDC’s Update to U.S. Medical Eligibility Criteria for Contraceptive Use, 2016: Updated Recommendations for the Use of Contraception Among Women at High Risk for HIV Infection.68

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Efavirenz (EFV)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, and Etonogestrel ImplantsIf efficacy is of primary importance, consider an alternative method (or a reliable method of barrier contraception in addition to this method).
Dosing Recommendation/Clinical Comment for DMPAaNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

COC

  • No effect on EE concentrations
  • ↓ active metabolites of norgestimate; LNG AUC ↓ 83% and norelgestromin AUC ↓ 64%37
  • Etonogestrel (in COC) C24h ↓ 61%43
  • Etonogestrel ↓ 79%; EE ↓ 59%54

DMPA

  • No effect on DMPA levels34,36

DMPA AUC ↓ 33-35% when coadministered with EFV, rifampin, and isoniazid. More frequent DMPA dosing may be appropriate.64

ENG Implant

  • ENG ↓ below the level necessary to prevent pregnancy (90 pg/mL) in 60% of people on EFV74
  • ↓ 49% in Etonogestrel concentration53
  • Etonogestrel AUC ↓ 63% to 82%59,70

LNG Implant

  • ↓ 61% LNG concentration53
  • LNG AUC ↓ 47%48
  • ↑ pregnancy incidence rate among women using LNG or ENG implants, more among ENG users61
  • LNG AUC ↓ 40–73% over 30 months of use62
  • Doubling the dose of LNG implant from 150 mg to 300 mg did not overcome the decrease in LNG concentration.58

LNG Emergency Contraception (Oral dosing)

  • LNG (emergency contraception) AUC ↓ 58%31
  • Cmax was 51% higher with 3 mg LNG (24.9 ng/mL) compared to 1.5 mg (15.1 ng/mL), and the 48-hour concentration was 66% higher (0.6 vs 0.3 ng/mL, respectively). Dose adjustment of LNG EC from 1.5 mg to 3 mg successfully increased LNG exposure on EFV-based ART32

Vaginally Administered Etonogestrel/EE (Vaginal Ring)

  • Etonogestrel ↓ 93% in CYP2B6 slow metabolizers and ↓ 75% in normal and intermediate metabolizers63
  • EE ↓ 75% in slow metabolizers and ↓ 41% in normal and intermediate metabolizers63

Changes in ARV Levels and/or Effects on HIV

COC

  • No effect on EFV concentrations37
  • EFV C12h ↓ 22%; was under therapeutic threshold in three of 16 subjects43

DMPA

  • No effect on HIV disease progression34,71,72
  • No effect on EFV concentrations34

LNG Implant

  • No effect on HIV disease progression48
Clinical Studies

COC

  • No difference in pregnancy rates60
  • Pregnancy rate was 13% higher in women using COCs and EFV than in women using COCs alone58,73
  • Progesterone >3 ng/mL (a surrogate for ovulation) in three of 16 women74
  • No ovulations37

DMPA

  • No increase in pregnancies34,58,60,72
  • Low endogenous progesterone, consistent with no ovulation34,36,72

Etonogestrel Implant

  • Pregnancy rate higher with EFV compared with no ART but still lower with implants than with other hormonal methods of contraception58
  • Presumptive ovulation in 5%70

Levonogestrel Implant

  • 12% pregnancy rate44
  • 15% pregnancy rate48
  • Pregnancy rate higher with EFV compared with no ART but still lower with implants than with other hormonal methods of contraception58
  • No increase in pregnancy rate60
Justification/Evidence for Recommendation

For COCs, some studies suggest higher pregnancy rate and ovulation rate and decreased progestin levels. EFV may decrease, but clinical significance unclear.

For DMPA, evidence does not show effects on pregnancy rate, ovulation, or DMPA levels. Also, no effect on HIV disease progression or EFV levels

More frequent DMPA dosing may be appropriate for women receiving rifampicin, INH, and EFV.

For implants, some studies suggest higher pregnancy rate and decreased hormone levels.

For vaginally administered etonogestrel/EE, PK evaluation showed that etonogestrel levels were 79% lower and EE levels were 59% lower in participants on EFV than in controls after 21 days.54

Etravirine (ETR)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

EE AUC ↑ 22%75

No significant effect on NE75

Clinical Studies

COC

  • No ovulations75
Justification/Evidence for Recommendation

For COCs, one study found no ovulations and no significant change in progestin levels.

No data on POPs.

Nevirapine (NVP)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

EE AUC ↓ 29%;76 no change in EE AUC77

NE AUC ↓ 18%76

Etonogestrel (in COC) C24h ↓ 22%43

DMPA

  • No significant change34

LNG Implant

  • LNG AUC ↑ 35%48
  • ↑ pregnancy incidence rate among women using LNG or ENG implants, more among ENG users61

Changes in ARV Levels and/or Effects on HIV

COC

  • No significant effect on NVP levels74,76,78

DMPA

  • No effect on HIV disease progression34,71,72,79

LNG Implant

  • No effect on HIV disease progression48,80
Clinical Studies

COC

  • No increase in pregnancy rate58,60,73,81,82
  • No ovulations74,77,82

DMPA

  • No increase in pregnancy rates58,60,72,81
  • Low serum progesterone, consistent with no ovulation34

Etonogestrel Implant

  • No increase in pregnancy rate58

LNG Implant

  • No increase in pregnancy rate44,48,58,60,80
Justification/Evidence for Recommendation

For COCs, evidence does not show effects on pregnancy rate or ovulations. Evidence demonstrated small decrease in progestin levels. No effect on NVP levels.

For DMPA, evidence does not show effects on pregnancy rate, ovulation, or DMPA levels. No effect on HIV disease progression.

For implants, evidence does not show effects on pregnancy rate or HIV disease progression.

Rilpivirine (Oral RPV)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

EE AUC ↑ 14%42

No significant change on NE42

Changes in ARV Levels and/or Effects on HIV

COC

  • No change in RPV levels compared to historical controls42
Clinical Studies

COC

  • No change in progesterone42
Justification/Evidence for Recommendation

For COCs, evidence does not show effects on ovulation or progestin levels. No change in RPV levels.

No data on POPs

Doravirine (DOR)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIVNo clinically significant interaction with EE and LNG83
Clinical StudiesN/A
Justification/Evidence for RecommendationNo clinical data
Ritonavir (RTV)-Boosted Protease Inhibitors (PIs)
Atazanavir/Ritonavir (ATV/r)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

EE AUC ↓ 19%84

Norgestimate AUC ↑ 85%84

POP

  • NE AUC ↑ 50%85

Vaginally Administered Etonogestrel/EE

  • Etonogestrel ↑ 71%
  • EE ↓ 38%54
Clinical StudiesN/A
Justification/Evidence for Recommendation

For COCs, increase in progestin levels seen in only one study. Using a COC with at least 35 mcg/day may decrease breakthrough bleeding.

For POPs, increase in progestin levels seen in only one study

RTV inhibits CYP3A4, which may increase contraceptive hormone levels.

Darunavir/Ritonavir (DRV/r)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, and Etonogestrel ImplantsIf efficacy is of primary importance, can consider an alternative method (or a reliable method of barrier contraception in addition to this method)
Dosing Recommendation/Clinical Comment for DMPAaNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

EE AUC ↓ 44%55

NE AUC ↓ 14%55

Clinical StudiesN/A
Justification/Evidence for Recommendation

For COCs, small decrease in progestin levels

No data on POPs

Lopinavir/Ritonavir (LPV/r)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

EE AUC ↓ 55%33

NE AUC ↓ 17%

Patch

  • EE AUC ↓ 45%33
  • Norelgestromin AUC ↑ 83%33

DMPA

  • DMPA AUC ↑ 46%46

Etonogestrel Implant

  • Etonogestrel AUC ↑ 52%70

Changes in ARV Levels and/or Effects on HIV

Patch

  • LPV/r ↓ 19%33

DMPA

  • No effect on HIV disease progression46
  • No change in LPV/r levels46
Clinical Studies

COC

  • Trend of increased pregnancy rate, but CIs overlap58

Patch

  • Low serum progesterone consistent with no ovulations (n = 8)33

DMPA

  • No pregnancies and no ovulations46
  • Trend of increased pregnancy rate, but CIs overlap58

Etonogestrel Implant

  • No increase in pregnancy rate58

LNG Implant

  • No increase in pregnancy rate44,58
Justification/Evidence for Recommendation

For COCs, nonsignificant increase in pregnancy rate. Small decrease in progestin level

For patch, no ovulations, and progestin levels increased

For DMPA, evidence shows no effect on pregnancy rate or ovulations. Progestin levels increased.

For implants, evidence shows no effect on pregnancy rate. Progestin levels increased.

Cobicistat (COBI)-Boosted Protease Inhibitors (PIs)
Atazanavir/Cobicistat (ATV/c)
Dosing Recommendation/Clinical Comment for COC/P/RContraindicated with drospirenone-containing hormonal contraceptives due to potential for hyperkalemia
Dosing Recommendation/Clinical Comment for POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

Drospirenone AUC ↑ 2.3-fold51

No change in LNG concentration

25% decrease in EE C2450

Clinical StudiesN/A
Justification/Evidence for RecommendationNo data on POPs
Darunavir/Cobicistat (DRV/c)
Dosing Recommendation/Clinical Comment for COC/P/RClinical monitoring is recommended when DRV/c is used in combination with drospirenone-containing COCs as a result of the potential for hyperkalemia.
Dosing Recommendation/Clinical Comment for POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

Drospirenone AUC 1.6-fold

EE AUC ↓ 30%51

Clinical StudiesN/A
Justification/Evidence for RecommendationNo data on POPs.
Protease Inhibitors (PIs) Without Ritonavir (RTV)
Atazanavir (ATV)
Dosing Recommendation/Clinical Comment for COC/P/RPrescribe oral contraceptive that contains no more than 30 mcg of EE or recommend alternative contraceptive method.
Dosing Recommendation/Clinical Comment for POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

COC

  • EE AUC ↑ 48%86
  • NE AUC ↑ 110%86
Clinical StudiesN/A
Justification/Evidence for Recommendation

For COCs, increased concentrations of estrogen and progestin, but the only data available are from the product label.

No data on POPs

CCR5 Antagonist
Maraviroc (MVC)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

COC

  • No significant effect on EE or LN87
Clinical StudiesN/A
Justification/Evidence for Recommendation

For COCs, no change in EE or progestin. No clinical data

No data on POPs

Integrase Strand Transfer Inhibitors (INSTIs)
Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIVNo significant drug interactions with EE or norgestimate
Clinical StudiesN/A
Justification/Evidence for RecommendationNo clinical data
Dolutegravir (DTG)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

COC

  • No significant effect on etonogestrel implants69
  • No significant effect on norgestimate or EE
  • No change in DTG AUC47
Clinical StudiesN/A
Justification/Evidence for Recommendation

For COCs, no change in EE or progestin. No clinical data

No data on POPs

Elvitegravir/Cobicistat (EVG/c)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

COC

  • Norgestimate AUC ↑ 126%
  • EE AUC ↓ 25%88,89
Clinical StudiesN/A
Justification/Evidence for Recommendation

When administered as the 4-drug regimen EVG/c/FTC/TDF, increases in progestin and a small decrease in EE were observed. No clinical data

No data on POPs

Raltegravir (RAL)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

COC

  • No change in EE
  • Norgestimate AUC ↑ 14%90
Clinical StudiesN/A
Justification/Evidence for Recommendation

For COCs, no change in EE and a small increase in progestin. No clinical data

No data on POPs.

Cabotegravir-Long Acting (CAB-LA)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection needed
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIVOral contraceptive use was associated with ↓ CAB-LA Cmax compared to women not on any hormonal contraception (GMR 0.75; 90%CI:0.59-0.93; P=0.033). However, oral contraceptive use did not result in significant differences in other CAB-LA PK parameters.
Clinical StudiesN/A
Justification/Evidence for RecommendationAlthough oral contraceptive use was associated with lower CAB-LA peak concentration, no other PK parameters PK parameters seen suggesting the association is not likely to be clinically significant.
a Because the hormonal levels achieved with DMPA are substantially higher than the levels that are required for contraception, any small reduction in hormonal level attributed to ARV drugs is unlikely to reduce contraceptive effectiveness.

Key to Symbols:
↑ = increase
↓ = decrease

Key: ART = antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; BIC = bictegravir; C12h = concentration at 12 hours post-dose; C24h = concentration at 24 hours post-dose; CDC = Centers for Disease Control and Prevention; CI = confidence interval; Cmax; = minimum plasma concentration; Cmin = minimum plasma concentration; COBI = cobicistat; COC = combined oral contraceptives; COC/P/R = COC/patch/ring; CYP = cytochrome P450; DMPA = depot medroxyprogesterone acetate; DOR = doravirine; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EE = ethinyl estradiol; EFV = efavirenz; ENG = etonogestrel; ETR = etravirine; EVG/c = elvitegravir/cobicistat; FTC = emtricitabine; INSTI = integrase strand transfer inhibitor; LNG = levonorgestrel; LPV/r = lopinavir/ritonavir; MVC = maraviroc; NE = norethindrone; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; POP = progesterone-only oral contraceptive pills; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate

Sources: Panel on Antiretroviral Guidelines for Adults and Adolescents; Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV; Table 24a, Table 24b, and Table 24d

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  75. Vieira CS, Bahamondes MV, de Souza RM, et al. Effect of antiretroviral therapy including lopinavir/ritonavir or efavirenz on etonogestrel-releasing implant pharmacokinetics in HIV-positive women. J Acquir Immune Defic Syndr. 2014;66(4):378-385. Available at: https://pubmed.ncbi.nlm.nih.gov/24798768
  76. Polis CB, Curtis KM. Use of hormonal contraceptives and HIV acquisition in women: a systematic review of the epidemiological evidence. Lancet Infect Dis. 2013;13(9):797-808. Available at: https://pubmed.ncbi.nlm.nih.gov/23871397.
  77. Watts DH, Park JG, Cohn SE, et al. Safety and tolerability of depot medroxyprogesterone acetate among HIV-infected women on antiretroviral therapy: ACTG A5093. Contraception. 2008;77(2):84-90. Available at: https://pubmed.ncbi.nlm.nih.gov/18226670.
  78. Clark RA, Theall K. Population-based study evaluating association between selected antiretroviral therapies and potential oral contraceptive failure. J Acquir Immune Defic Syndr. 2004;37(1):1219-1220. Available at: https://pubmed.ncbi.nlm.nih.gov/15319685.
  79. Landolt NK, Phanuphak N, Ubolyam S, et al. Efavirenz, in contrast to nevirapine, is associated with unfavorable progesterone and antiretroviral levels when coadministered with combined oral contraceptives. J Acquir Immune Defic Syndr. 2013;62(5):534-539. Available at: https://pubmed.ncbi.nlm.nih.gov/23187949.
  80. Scholler-Gyure M, Kakuda TN, Woodfall B, et al. Effect of steady-state etravirine on the pharmacokinetics and pharmacodynamics of ethinylestradiol and norethindrone. Contraception. 2009;80(1):44-52. Available at: http://ac.els-cdn.com/S0010782409000262/1-s2.0-S0010782409000262-main.pdf?_tid=50ea57a0-6797-11e5-8db9-00000aab0f01&acdnat=1443633710_360a599a6e8d2fa152528b542d290cdb.
  81. Mildvan D, Yarrish R, Marshak A, et al. Pharmacokinetic interaction between nevirapine and ethinyl estradiol/norethindrone when administered concurrently to HIV-infected women. J Acquir Immune Defic Syndr. 2002;29(5):471-477. Available at: https://pubmed.ncbi.nlm.nih.gov/11981363.
  82. Stuart GS, Moses A, Corbett A, et al. Combined oral contraceptives and antiretroviral PK/PD in Malawian women: pharmacokinetics and pharmacodynamics of a combined oral contraceptive and a generic combined formulation antiretroviral in Malawi. J Acquir Immune Defic Syndr. 2011;58(2):e40-43. Available at: https://pubmed.ncbi.nlm.nih.gov/21921726.
  83. Muro E, Droste JA, Hofstede HT, et al. Nevirapine plasma concentrations are still detectable after more than 2 weeks in the majority of women receiving single-dose nevirapine: implications for intervention studies. J Acquir Immune Defic Syndr. 2005;39(4):419-421. Available at: https://pubmed.ncbi.nlm.nih.gov/16010163.
  84. Day S, Graham SM, Masese LN, et al. A prospective cohort study of the effect of depot medroxyprogesterone acetate on detection of plasma and cervical HIV-1 in women initiating and continuing antiretroviral therapy. J Acquir Immune Defic Syndr. 2014;66(4):452-456. Available at: https://pubmed.ncbi.nlm.nih.gov/24798764.
  85. Hubacher D, Liku J, Kiarie J, et al. Effect of concurrent use of anti-retroviral therapy and levonorgestrel sub-dermal implant for contraception on CD4 counts: a prospective cohort study in Kenya. J Int AIDS Soc. 2013;16:18448. Available at: https://pubmed.ncbi.nlm.nih.gov/23458102.
  86. Myer L, Carter RJ, Katyal M, et al. Impact of antiretroviral therapy on incidence of pregnancy among HIV-infected women in sub-Saharan Africa: a cohort study. PLoS Med. 2010;7(2):e1000229. Available at: https://pubmed.ncbi.nlm.nih.gov/20161723.
  87. Nanda K, Delany-Moretlwe S, Dube K, et al. Nevirapine-based antiretroviral therapy does not reduce oral contraceptive effectiveness. AIDS. 2013;27 Suppl 1:S17-25. Available at: https://pubmed.ncbi.nlm.nih.gov/24088680.
  88. Khalilieh SG, Yee KL, Sanchez RI, et al. Doravirine and the potential for CYP3A-mediated drug-drug interactions. Antimicrob Agents Chemother. 2019;63(5):e02016-02018. Available at: https://pubmed.ncbi.nlm.nih.gov/30783000.
  89. Zhang J, Chung E, Yones C, et al. The effect of atazanavir/ritonavir on the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and norgestimate in healthy women. Antivir Ther. 2011;16(2):157-164. Available at: https://pubmed.ncbi.nlm.nih.gov/21447864.
  90. DuBois BN, Atrio J, Stanczyk FZ, Cherala G. Increased exposure of norethindrone in HIV+ women treated with ritonavir-boosted atazanavir therapy. Contraception. 2015;91(1):71-75. Available at: https://pubmed.ncbi.nlm.nih.gov/25245190.
  91. Atazanavir (Reyataz) [package insert]. Food and Drug Administration. 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021567s044,206352s008lbl.pdf.
  92. Abel S, Russell D, Whitlock LA, et al. Effect of maraviroc on the pharmacokinetics of midazolam, lamivudine/zidovudine, and ethinyloestradiol/levonorgestrel in healthy volunteers. Br J Clin Pharmacol. 2008;65 Suppl 1:19-26. Available at: https://pubmed.ncbi.nlm.nih.gov/18333862.
  93. Stribild (elvitegravir, cobicitstat, emtricitabine, tenofovir disaproxil fumarate) [package insert]. Food and Drug Administration. 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/203100s035lbl.pdf.
  94. Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) [package insert]. Food and Drug Administration. 2021. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/207561s025lbl.pdf.
  95. Anderson MS, Hanley WD, Moreau AR, et al. Effect of raltegravir on estradiol and norgestimate plasma pharmacokinetics following oral contraceptive administration in healthy women. Br J Clin Pharmacol. 2011;71(4):616-620. Available at: https://pubmed.ncbi.nlm.nih.gov/21395656.

Prepregnancy Counseling and Care for People of Childbearing Age with HIV

Overview

Panel's Recommendations
  • Discuss reproductive desires and plans with all people with HIV who are of childbearing potential on an ongoing basis throughout the course of their care (AIII).
  • Provide information about effective and appropriate contraceptive methods to people who do not currently desire pregnancy (AI). Offer all contraceptive methods or refer for contraceptive services. Individuals with HIV can use all available contraceptive methods (e.g., pill, patch ring, injection, implant); however, the presence of other medical co-morbidities and drug -drug interactions between hormonal contraceptives, antiretroviral (ARV) drugs, and other medications should be considered (see Table 3) (AII). This information may help support shared decision-making about acceptable contraception options for people not currently desiring pregnancy.
  • During prepregnancy counseling, provide information on safer sex and ask about the use of alcohol, nicotine products, and other substances. Provide or refer to evidence-based interventions for substance use disorder, including medication-assisted treatment for opioid use disorder (e.g., methadone, buprenorphine), and counsel people on how to manage health risks (e.g., by accessing a syringe services program) when indicated. (AII).
  • Provide education and counseling about interventions to prevent perinatal HIV transmission, including antiretroviral therapy (ART). Explain that people with HIV should attain maximum viral suppression before attempting conception, for their own health, to prevent sexual HIV transmission to partners without HIV (AI), and to minimize the risk of in utero HIV transmission to the infant (AI). When fully suppressive ART is started before pregnancy and undetectable viral load is maintained throughout pregnancy and at delivery, the risk of HIV transmission to the infant is extremely low (<1%).
  • For people with HIV who are considering or planning a pregnancy, begin to provide patient-centered, evidence-based counseling to support shared decision making about infant feeding (AIII) (see Infant Feeding for Individuals with HIV in the United States).Information and plans for infant feeding should be reviewed throughout pregnancy and again after delivery.
  • When selecting or evaluating an ARV regimen for people of childbearing potential with HIV, consider a regimen’s effectiveness, changes in ARV pharmacokinetics in the second and third trimesters of pregnancy, a person’s hepatitis B status, and the possible adverse outcomes for the pregnant person and their fetus (AII). See Teratogenicity and Recommendations for Use of Antiretroviral Drugs During Pregnancy: Overview for more information. The Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission emphasizes the importance of counseling and shared decision-making regarding all ARV regimens for people with HIV (AIII).
Rating of Recommendations: A = Strong; B = Moderate; C = Optional

Rating of Evidence: I = One or more randomized trials with clinical outcomes and/or validated laboratory endpoints; II = One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = Expert opinion

Table 3. Drug Interactions Between Antiretroviral Agents and Hormonal Contraceptives

Note: All recommendations in this table are based on consensus expert opinion. Additional information can be found in CDC’s Update to U.S. Medical Eligibility Criteria for Contraceptive Use, 2016: Updated Recommendations for the Use of Contraception Among Women at High Risk for HIV Infection.68

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Efavirenz (EFV)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, and Etonogestrel ImplantsIf efficacy is of primary importance, consider an alternative method (or a reliable method of barrier contraception in addition to this method).
Dosing Recommendation/Clinical Comment for DMPAaNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

COC

  • No effect on EE concentrations
  • ↓ active metabolites of norgestimate; LNG AUC ↓ 83% and norelgestromin AUC ↓ 64%37
  • Etonogestrel (in COC) C24h ↓ 61%43
  • Etonogestrel ↓ 79%; EE ↓ 59%54

DMPA

  • No effect on DMPA levels34,36

DMPA AUC ↓ 33-35% when coadministered with EFV, rifampin, and isoniazid. More frequent DMPA dosing may be appropriate.64

ENG Implant

  • ENG ↓ below the level necessary to prevent pregnancy (90 pg/mL) in 60% of people on EFV74
  • ↓ 49% in Etonogestrel concentration53
  • Etonogestrel AUC ↓ 63% to 82%59,70

LNG Implant

  • ↓ 61% LNG concentration53
  • LNG AUC ↓ 47%48
  • ↑ pregnancy incidence rate among women using LNG or ENG implants, more among ENG users61
  • LNG AUC ↓ 40–73% over 30 months of use62
  • Doubling the dose of LNG implant from 150 mg to 300 mg did not overcome the decrease in LNG concentration.58

LNG Emergency Contraception (Oral dosing)

  • LNG (emergency contraception) AUC ↓ 58%31
  • Cmax was 51% higher with 3 mg LNG (24.9 ng/mL) compared to 1.5 mg (15.1 ng/mL), and the 48-hour concentration was 66% higher (0.6 vs 0.3 ng/mL, respectively). Dose adjustment of LNG EC from 1.5 mg to 3 mg successfully increased LNG exposure on EFV-based ART32

Vaginally Administered Etonogestrel/EE (Vaginal Ring)

  • Etonogestrel ↓ 93% in CYP2B6 slow metabolizers and ↓ 75% in normal and intermediate metabolizers63
  • EE ↓ 75% in slow metabolizers and ↓ 41% in normal and intermediate metabolizers63

Changes in ARV Levels and/or Effects on HIV

COC

  • No effect on EFV concentrations37
  • EFV C12h ↓ 22%; was under therapeutic threshold in three of 16 subjects43

DMPA

  • No effect on HIV disease progression34,71,72
  • No effect on EFV concentrations34

LNG Implant

  • No effect on HIV disease progression48
Clinical Studies

COC

  • No difference in pregnancy rates60
  • Pregnancy rate was 13% higher in women using COCs and EFV than in women using COCs alone58,73
  • Progesterone >3 ng/mL (a surrogate for ovulation) in three of 16 women74
  • No ovulations37

DMPA

  • No increase in pregnancies34,58,60,72
  • Low endogenous progesterone, consistent with no ovulation34,36,72

Etonogestrel Implant

  • Pregnancy rate higher with EFV compared with no ART but still lower with implants than with other hormonal methods of contraception58
  • Presumptive ovulation in 5%70

Levonogestrel Implant

  • 12% pregnancy rate44
  • 15% pregnancy rate48
  • Pregnancy rate higher with EFV compared with no ART but still lower with implants than with other hormonal methods of contraception58
  • No increase in pregnancy rate60
Justification/Evidence for Recommendation

For COCs, some studies suggest higher pregnancy rate and ovulation rate and decreased progestin levels. EFV may decrease, but clinical significance unclear.

For DMPA, evidence does not show effects on pregnancy rate, ovulation, or DMPA levels. Also, no effect on HIV disease progression or EFV levels

More frequent DMPA dosing may be appropriate for women receiving rifampicin, INH, and EFV.

For implants, some studies suggest higher pregnancy rate and decreased hormone levels.

For vaginally administered etonogestrel/EE, PK evaluation showed that etonogestrel levels were 79% lower and EE levels were 59% lower in participants on EFV than in controls after 21 days.54

Etravirine (ETR)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

EE AUC ↑ 22%75

No significant effect on NE75

Clinical Studies

COC

  • No ovulations75
Justification/Evidence for Recommendation

For COCs, one study found no ovulations and no significant change in progestin levels.

No data on POPs.

Nevirapine (NVP)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

EE AUC ↓ 29%;76 no change in EE AUC77

NE AUC ↓ 18%76

Etonogestrel (in COC) C24h ↓ 22%43

DMPA

  • No significant change34

LNG Implant

  • LNG AUC ↑ 35%48
  • ↑ pregnancy incidence rate among women using LNG or ENG implants, more among ENG users61

Changes in ARV Levels and/or Effects on HIV

COC

  • No significant effect on NVP levels74,76,78

DMPA

  • No effect on HIV disease progression34,71,72,79

LNG Implant

  • No effect on HIV disease progression48,80
Clinical Studies

COC

  • No increase in pregnancy rate58,60,73,81,82
  • No ovulations74,77,82

DMPA

  • No increase in pregnancy rates58,60,72,81
  • Low serum progesterone, consistent with no ovulation34

Etonogestrel Implant

  • No increase in pregnancy rate58

LNG Implant

  • No increase in pregnancy rate44,48,58,60,80
Justification/Evidence for Recommendation

For COCs, evidence does not show effects on pregnancy rate or ovulations. Evidence demonstrated small decrease in progestin levels. No effect on NVP levels.

For DMPA, evidence does not show effects on pregnancy rate, ovulation, or DMPA levels. No effect on HIV disease progression.

For implants, evidence does not show effects on pregnancy rate or HIV disease progression.

Rilpivirine (Oral RPV)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

EE AUC ↑ 14%42

No significant change on NE42

Changes in ARV Levels and/or Effects on HIV

COC

  • No change in RPV levels compared to historical controls42
Clinical Studies

COC

  • No change in progesterone42
Justification/Evidence for Recommendation

For COCs, evidence does not show effects on ovulation or progestin levels. No change in RPV levels.

No data on POPs

Doravirine (DOR)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIVNo clinically significant interaction with EE and LNG83
Clinical StudiesN/A
Justification/Evidence for RecommendationNo clinical data
Ritonavir (RTV)-Boosted Protease Inhibitors (PIs)
Atazanavir/Ritonavir (ATV/r)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

EE AUC ↓ 19%84

Norgestimate AUC ↑ 85%84

POP

  • NE AUC ↑ 50%85

Vaginally Administered Etonogestrel/EE

  • Etonogestrel ↑ 71%
  • EE ↓ 38%54
Clinical StudiesN/A
Justification/Evidence for Recommendation

For COCs, increase in progestin levels seen in only one study. Using a COC with at least 35 mcg/day may decrease breakthrough bleeding.

For POPs, increase in progestin levels seen in only one study

RTV inhibits CYP3A4, which may increase contraceptive hormone levels.

Darunavir/Ritonavir (DRV/r)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, and Etonogestrel ImplantsIf efficacy is of primary importance, can consider an alternative method (or a reliable method of barrier contraception in addition to this method)
Dosing Recommendation/Clinical Comment for DMPAaNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

EE AUC ↓ 44%55

NE AUC ↓ 14%55

Clinical StudiesN/A
Justification/Evidence for Recommendation

For COCs, small decrease in progestin levels

No data on POPs

Lopinavir/Ritonavir (LPV/r)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

EE AUC ↓ 55%33

NE AUC ↓ 17%

Patch

  • EE AUC ↓ 45%33
  • Norelgestromin AUC ↑ 83%33

DMPA

  • DMPA AUC ↑ 46%46

Etonogestrel Implant

  • Etonogestrel AUC ↑ 52%70

Changes in ARV Levels and/or Effects on HIV

Patch

  • LPV/r ↓ 19%33

DMPA

  • No effect on HIV disease progression46
  • No change in LPV/r levels46
Clinical Studies

COC

  • Trend of increased pregnancy rate, but CIs overlap58

Patch

  • Low serum progesterone consistent with no ovulations (n = 8)33

DMPA

  • No pregnancies and no ovulations46
  • Trend of increased pregnancy rate, but CIs overlap58

Etonogestrel Implant

  • No increase in pregnancy rate58

LNG Implant

  • No increase in pregnancy rate44,58
Justification/Evidence for Recommendation

For COCs, nonsignificant increase in pregnancy rate. Small decrease in progestin level

For patch, no ovulations, and progestin levels increased

For DMPA, evidence shows no effect on pregnancy rate or ovulations. Progestin levels increased.

For implants, evidence shows no effect on pregnancy rate. Progestin levels increased.

Cobicistat (COBI)-Boosted Protease Inhibitors (PIs)
Atazanavir/Cobicistat (ATV/c)
Dosing Recommendation/Clinical Comment for COC/P/RContraindicated with drospirenone-containing hormonal contraceptives due to potential for hyperkalemia
Dosing Recommendation/Clinical Comment for POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

Drospirenone AUC ↑ 2.3-fold51

No change in LNG concentration

25% decrease in EE C2450

Clinical StudiesN/A
Justification/Evidence for RecommendationNo data on POPs
Darunavir/Cobicistat (DRV/c)
Dosing Recommendation/Clinical Comment for COC/P/RClinical monitoring is recommended when DRV/c is used in combination with drospirenone-containing COCs as a result of the potential for hyperkalemia.
Dosing Recommendation/Clinical Comment for POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

Drospirenone AUC 1.6-fold

EE AUC ↓ 30%51

Clinical StudiesN/A
Justification/Evidence for RecommendationNo data on POPs.
Protease Inhibitors (PIs) Without Ritonavir (RTV)
Atazanavir (ATV)
Dosing Recommendation/Clinical Comment for COC/P/RPrescribe oral contraceptive that contains no more than 30 mcg of EE or recommend alternative contraceptive method.
Dosing Recommendation/Clinical Comment for POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

COC

  • EE AUC ↑ 48%86
  • NE AUC ↑ 110%86
Clinical StudiesN/A
Justification/Evidence for Recommendation

For COCs, increased concentrations of estrogen and progestin, but the only data available are from the product label.

No data on POPs

CCR5 Antagonist
Maraviroc (MVC)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

COC

  • No significant effect on EE or LN87
Clinical StudiesN/A
Justification/Evidence for Recommendation

For COCs, no change in EE or progestin. No clinical data

No data on POPs

Integrase Strand Transfer Inhibitors (INSTIs)
Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIVNo significant drug interactions with EE or norgestimate
Clinical StudiesN/A
Justification/Evidence for RecommendationNo clinical data
Dolutegravir (DTG)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

COC

  • No significant effect on etonogestrel implants69
  • No significant effect on norgestimate or EE
  • No change in DTG AUC47
Clinical StudiesN/A
Justification/Evidence for Recommendation

For COCs, no change in EE or progestin. No clinical data

No data on POPs

Elvitegravir/Cobicistat (EVG/c)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

COC

  • Norgestimate AUC ↑ 126%
  • EE AUC ↓ 25%88,89
Clinical StudiesN/A
Justification/Evidence for Recommendation

When administered as the 4-drug regimen EVG/c/FTC/TDF, increases in progestin and a small decrease in EE were observed. No clinical data

No data on POPs

Raltegravir (RAL)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection is needed.
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV

COC

  • No change in EE
  • Norgestimate AUC ↑ 14%90
Clinical StudiesN/A
Justification/Evidence for Recommendation

For COCs, no change in EE and a small increase in progestin. No clinical data

No data on POPs.

Cabotegravir-Long Acting (CAB-LA)
Dosing Recommendation/Clinical Comment for COC/P/R, POPs, DMPAa, Etonogestrel ImplantsNo additional contraceptive protection needed
Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIVOral contraceptive use was associated with ↓ CAB-LA Cmax compared to women not on any hormonal contraception (GMR 0.75; 90%CI:0.59-0.93; P=0.033). However, oral contraceptive use did not result in significant differences in other CAB-LA PK parameters.
Clinical StudiesN/A
Justification/Evidence for RecommendationAlthough oral contraceptive use was associated with lower CAB-LA peak concentration, no other PK parameters PK parameters seen suggesting the association is not likely to be clinically significant.
a Because the hormonal levels achieved with DMPA are substantially higher than the levels that are required for contraception, any small reduction in hormonal level attributed to ARV drugs is unlikely to reduce contraceptive effectiveness.

Key to Symbols:
↑ = increase
↓ = decrease

Key: ART = antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; BIC = bictegravir; C12h = concentration at 12 hours post-dose; C24h = concentration at 24 hours post-dose; CDC = Centers for Disease Control and Prevention; CI = confidence interval; Cmax; = minimum plasma concentration; Cmin = minimum plasma concentration; COBI = cobicistat; COC = combined oral contraceptives; COC/P/R = COC/patch/ring; CYP = cytochrome P450; DMPA = depot medroxyprogesterone acetate; DOR = doravirine; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EE = ethinyl estradiol; EFV = efavirenz; ENG = etonogestrel; ETR = etravirine; EVG/c = elvitegravir/cobicistat; FTC = emtricitabine; INSTI = integrase strand transfer inhibitor; LNG = levonorgestrel; LPV/r = lopinavir/ritonavir; MVC = maraviroc; NE = norethindrone; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; POP = progesterone-only oral contraceptive pills; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate

Sources: Panel on Antiretroviral Guidelines for Adults and Adolescents; Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV; Table 24a, Table 24b, and Table 24d

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